This application requests funds for continuation of a Cell Physiology Training Program that has been developed over the last decade with the rebuilding of the Department of Physiology and Biophysics at CWRU. Compared to the original application five years ago, the departmental research base, number of active faculty members, and trainee pool provided by departmental graduate students have nearly doubled in size. The objective of this Training program is to provide outstanding training to a few, highly qualified and motivated biomedical scientists in the discipline of cellular and molecular physiology and pathophysiology. Cell physiology is broadly defined as the field that is concerned with the functions of cellular structures and molecules. Major emphasis is placed on cellular regulatory biology consisting of intracellular signaling, ion transport, and gene regulation. Predoctoral trainees and post-doctoral trainees with M.D. degrees are enrolled in a Ph.D. program in either cell physiology or biophysics/bioengineering; post-doctoral trainees with a Ph.D. complete their training predominantly through guided laboratory research. The total pool of predoctoral trainees enrolled in departmental programs and eligible for this NIH Training program is currently 45 and 9-12 new, eligible students start in the programs each year. There is an even larger pool of post-doctoral students who apply for training positions. The Training Faculty of this Program is composed of 24 outstanding scientists derived from the faculty of the Department of Physiology and Biophysics. Cell physiology is the major focus of the Department which has over 60 active members, including both primary and secondary appointments as the Department has become the center for this discipline in Cleveland. Rigorous predoctoral training is provided through the graduate programs of the Department of Physiology and Biophysics and includes a set of foundation and advanced courses specifically designed for cell physiology students, laboratory rotations, seminars, and guided research. Progress of trainees t=is tightly monitored whereby one of the quality checks consists of the requirement that students publish at least two first-authored articles in the premier, peer-reviewed journal of their respective field. The Program at the time of the renewal provides expanded training opportunities in a wide range of the methodologies that constitute the basic research approaches in the field of cell physiology (chemical and electrical signal transduction, ion and non-electrolyte membrane transport, regulation of gene expression, structure-function relationship of proteins, bioenergetics, motility) while at the same time the number of highly qualified applicants has greatly increased.